Nicotine delivery and relief of craving after consumption of European JUUL e-cigarettes prior and after pod modification

Mallock, Nadja; Rabenstein, Andrea; Gernun, Solveig; Laux, Peter; Hutzler, Christoph; Karch, Susanne; Koller, Gabriele; Henkler-Stephani, Frank; Parr, Maria Kristina; Pogarell, Oliver; Luch, Andreas; Rüther, Tobias

doi:10.1038/s41598-021-91593-6

Cited by 9 publications

(15 citation statements)

References 40 publications

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“…The addictiveness of tobacco products depends both on the nicotine dose and the rapidity of nicotine delivery. − In Europe, the limitation of nicotine to 20 mg/mL imposed by the European Tobacco Product Directive may mitigate the craving satisfaction experienced by users for nicotine content superior to 18 mg/mL but also may suggest a lower addiction potential. , Still, nicotine salts may considerably modify nicotine pharmacokinetics, thus addictiveness, even at lower doses through other mechanisms such as (1) a change of nicotine cellular uptake induced by protonated form compared to free-base form, (2) a modification in the gas/particle repartition of nicotine in the aerosol because the gaseous state or dissolved in a droplet of nicotine is a possible important factor of nicotine pharmacokinetics, and (3) the throat hit suppression/reduction enable deeper lung inhalation of the aerosol and a better aerosol deposition in the alveolar region favoring a more rapid or greater systemic passage. Additionally, NicH + could directly impact lung biological integrity.…”

Section: Introductionmentioning

confidence: 99%

Toward Better Characterization of a Free-Base Nicotine Fraction in e-Liquids and Aerosols

Bourgart

Leclerc

Pourchez

et al. 2022

Chem. Res. Toxicol.

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Given that nicotine salts are a growing market, methods are needed to characterize nicotine forms in e-cigarette vaping products. By lowering the free-base nicotine fraction (α fb ) in favor of protonated forms, the addition of organic acids to the eliquid mix greatly modulates nicotine pharmacokinetics and improves vapers' craving. This research investigated (1) the performance of pH measurement, liquid−liquid extraction (LLE), and acid/nicotine molar ratio calculation methods for α fb estimation in 6 nicotine benzoate and nicotine salicylate e-liquids and (2) nicotine protonation in the aerosol post vaporization. Aerosols were generated with a JUUL device and another mod-pod on a vaping machine to assess device effects. E-liquid and aerosol samples were then analyzed after further analytical optimization of previous methods and careful consideration of biases. Globally, performances were comparable between methods. α fb accounted for less than 5% of nicotine content regardless of experimental conditions. α fb were consistent between e-liquids and aerosols irrespective of e-cigarette devices. Hence, e-liquids are adequate surrogates for aerosols, facilitating the establishment of regulations. pH measurement is one of the most used methods and enables the establishment of relative scales for e-liquid classification but lacks automation possibility. Until now, the extent of sample dilution remained arbitrary. The dilution factor was fixed at 10, as usually achieved, since no effect of dilution was noted. pH values ranged from 5.3 to 6.3 in accordance with the literature. By contrast, LLE relies on the specificity of organic solvent for free-base nicotine extraction, causing discrepancies in previous studies. Here, the results were similar to α fb values from pH determination. Yet, LLE presented the highest variability and was the most time-consuming protocol. Finally, α fb calculation from molar ratio was the most robust and versatile method. Estimations can be made in silico from reported composition data and/or after liquid chromatography routine analysis.

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Section: Introductionmentioning

confidence: 99%

Toward Better Characterization of a Free-Base Nicotine Fraction in e-Liquids and Aerosols

Bourgart

Leclerc

Pourchez

et al. 2022

Chem. Res. Toxicol.

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“…Baseline characteristics for all 32 participants are presented in Table 1 and the flow of participants through the study is shown in Figure 1. The nicotine levels for the three groups with the corresponding numbers of participants are shown in Figure 2 36 .…”

Section: Baseline Characteristicsmentioning

confidence: 99%

Cardiovascular functions and arterial stiffness after JUUL use

Gernun¹,

Franzen²,

Mallock³

et al. 2022

Tob. Induc. Dis.

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INTRODUCTION The rapid growth in the e-cigarette market after the launch of JUUL e-cigarettes led to much discussion on the potential benefits and risks of pods, JUUL devices, and conventional e-cigarettes compared with combustible cigarettes. Independent data are required to assess the effects of these products on cardiovascular surrogate parameters and cardiovascular risk. METHODS We conducted a single-center three-arm study comparing combustible cigarettes with JUUL e-cigarettes with the old and new technology. We recruited 32 participants who were active smokers (n=15) or vapers (n=17) and performed a total of 39 measurements before and 5, 15, and 30 minutes, after participants smoked a combustible cigarette or vaped a JUUL e-cigarette with the new or old technology. Measurements included peripheral and central blood pressures and parameters of arterial stiffness, including pulse wave velocity and augmentation index. RESULTS Peripheral systolic blood pressure, central blood pressure, and peripheral pulse rate increased significantly in all three groups (each p<0.05). Heart rate (HR) changes lasted significantly longer than blood pressure changes. The augmentation index and pulse wave velocity increased in all three groups, and a multivariate analysis of variance showed that the increases were independent of systolic blood pressure, sex, age, device, and HR. CONCLUSIONS Changes in blood pressure and arterial stiffness are similar after cigarette smoking and JUUL use. These changes may be associated with an increased cardiovascular risk compared with no product use. However, a longterm follow-up evaluation of JUUL use and a head-to-head comparison with conventional e-cigarettes are still needed.

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“…Reasons for this were discussed and include the social media marketing strategy, the selection of appealing flavors, product features, and the high nicotine delivery of the US version [ 16 , 17 , 18 , 19 , 20 ]. While we have showed that the European version delivers much less nicotine than a conventional cigarette in a study applying a pre-directed puffing protocol [ 21 ], it is unclear what nicotine levels are reached when consumers use the products in their own pattern. It was hypothesized that pod e-cigs may be used differently than known for older generation e-cigs.…”

Section: Introductionmentioning

confidence: 99%

Usage Pattern and Nicotine Delivery during Ad Libitum Consumption of Pod E-Cigarettes and Heated Tobacco Products

Rabenstein

Rahofer

Vukas

et al. 2023

Toxics

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Many different nicotine delivery products, such as e-cigarettes (e-cigs) or heated tobacco products (HTPs), are available on the market. To better understand these products, it is crucial to learn how consumers use them and how much nicotine they deliver. Therefore, a pod e-cig, an HTP, and a conventional cigarette (CC) were each used by 15 experienced users of the respective product category for 90 min without special use instructions (“ad libitum”). Sessions were video recorded to analyze usage patterns and puff topography. At defined time points, blood was sampled to determine nicotine concentrations, and subjective effects were inquired about using questionnaires. During the study period, the CC and HTP groups averaged the same number of consumption units (both 4.2 units). In the pod e-cig group, the highest number of puffs was taken (pod e-cig 71.9; HTP: 52.2; CC: 42.3 puffs) with the most extended mean puff duration (pod e-cig: 2.8 s; HTP: 1.9 s; CC: 1.8 s). Pod e-cigs were predominantly used with single puffs or in short clusters of 2–5 puffs. The maximum plasma nicotine concentration was highest for CCs, followed by HTPs, and then pod e-cigs with 24.0, 17.7, and 8.0 ng/mL, respectively. Craving was reduced by all products. The results suggest that the high nicotine delivery known for tobacco-containing products (CCs and HTPs) may not be needed for non-tobacco-containing products (pod e-cigs) to satisfy cravings in experienced users.

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Nicotine delivery and relief of craving after consumption of European JUUL e-cigarettes prior and after pod modification

Cited by 9 publications

References 40 publications

Toward Better Characterization of a Free-Base Nicotine Fraction in e-Liquids and Aerosols

Toward Better Characterization of a Free-Base Nicotine Fraction in e-Liquids and Aerosols

Cardiovascular functions and arterial stiffness after JUUL use

Usage Pattern and Nicotine Delivery during Ad Libitum Consumption of Pod E-Cigarettes and Heated Tobacco Products

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